Medical School, Nankai University, Tianjin, China.
The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, China.
Brain Behav Immun. 2021 Oct;97:68-78. doi: 10.1016/j.bbi.2021.06.015. Epub 2021 Jul 2.
Depression has a growing impact on public health. Accumulating evidence supports an association between depression and increased immune system activity. IL-10 is a key cytokine that inhibits excessive inflammatory responses and is related to the anti-inflammatory and protective functions of the central nervous system (CNS). Cx3cr1IL-10 mice were used in our study. We aimed to identify the role of IL-10 in microglia in depression and anxiety-like behavior. We performed a series of behavioral tests on the mice; the Cx3cr1IL-10 male mice showed depression- and anxiety-like behavior compared with the littermates. The expression of transient receptor potential canonical 5 (TRPC5) decreased in both the medial prefrontal cortex (mPFC) and amygdala regions. The cytokines IL-1β and IL-6 increased, and IL-10 was decreased by western blotting. The knockout mice showed different trends in the effects of synaptic proteins. In the mPFC, IL-10 knockout induced a decrease in NR2B and synaptophysin; in the amygdala region, there was a significant increase in NR2B and PSD95. IL-10 knockout from microglia induced a decrease in GAD67 and parvalbumin (Pv) in the mPFC, but not in the amygdala. Our results showed enhanced depression and anxiety-like behavior in the Cx3cr1 IL-10 mice, which could be related to an imbalance in local excitatory and inhibitory transmission, as well as neuroinflammation in the mPFC and amygdala. This imbalance was associated with increased local inflammation. Although many studies have demonstrated the role of TRPC channels in emotional responses, our study showed that TRPC was not involved in this process in Cx3cr1IL-10 mice.
抑郁症对公共健康的影响日益严重。越来越多的证据支持抑郁症与免疫系统活性增加之间存在关联。白细胞介素-10 (IL-10) 是一种关键的细胞因子，可抑制过度的炎症反应，并与中枢神经系统 (CNS) 的抗炎和保护功能有关。在我们的研究中使用了 Cx3cr1IL-10 小鼠。我们旨在确定 IL-10 在抑郁症和焦虑样行为中小胶质细胞中的作用。我们对小鼠进行了一系列行为测试；与同窝仔相比，Cx3cr1IL-10 雄性小鼠表现出抑郁和焦虑样行为。瞬时受体电位经典型 5 (TRPC5) 的表达在 mPFC 和杏仁核区域均降低。细胞因子 IL-1β 和 IL-6 增加，而 IL-10 通过 Western blot 减少。敲除小鼠显示突触蛋白的影响有不同的趋势。在 mPFC 中，IL-10 敲除导致 NR2B 和突触小体蛋白减少；在杏仁核区域，NR2B 和 PSD95 显著增加。mPFC 中小胶质细胞中 IL-10 的敲除导致 GAD67 和 parvalbumin (Pv) 减少，但在杏仁核中没有。我们的结果显示，Cx3cr1 IL-10 小鼠表现出增强的抑郁和焦虑样行为，这可能与 mPFC 和杏仁核中局部兴奋性和抑制性传递失衡以及神经炎症有关。这种失衡与局部炎症增加有关。尽管许多研究表明 TRPC 通道在情绪反应中的作用，但我们的研究表明，在 Cx3cr1IL-10 小鼠中，TRPC 不参与这一过程。
